Cryo-EM Studies of SARS-CoV-2 Antibody Complexes

The Aaron Diamond AIDS Research Center (ADARC) at Columbia University has identified numerous neutralizing antibodies from convalescent COVID-19 donors at Columbia University Medical Center. Some of these antibodies are highly potent, and could provide the basis for monoclonal antibody therapeutics or "passive" immunization. Nevertheless, the mechanisms by which these antibodies neutralize the virus, and the viral epitopes targeted remain unknown. We have begun single-particle cryo-EM studies with our Titan Krios at Columbia's Zuckerman Institute, and have produced our first 3D reconstructions of SARS-CoV-2 spike protein in complex with neutralizing antibodies. GPU computing power has become a major stumbling block in these studies. Sequence analysis of hundreds of ADARC-isolated antibodies reveal several "multi-donor" antibody classes, likely to represent immunological solutions to SARS-CoV-2 neutralization commonly elicited in the population. Based on these observations, we expect to need to determine well over a dozen antibody-complex structures, with a corresponding need for increased GPU-based computing. ADARC has previously developed antibody therapeutics to clinical approval, and the proposed work will accelerate the development of our SARS-CoV-2 neutralizing antibodies to accelerated clinical trials.